@misc{oai:repo.qst.go.jp:00078226,
 author = {Takuwa, Hiroyuki and Takuwa, Hiroyuki},
 month = {Sep},
 note = {Accumulations of tau protein aggregates are mechanistically implicated in Alzheimer’s disease and Parkinson's disease, respectively. Several researchers have recently demonstrated that tau proteins can transfer between neurons in a manner dependent on neural activations. Therefore, continuous removal of tau protein released from activated neurons is important for homeostatic protection of neurons against tau-induced toxicities. In the present study, we investigated mechanisms and pathways involved in the clearance of tau assemblie from the brain using PBB3 as bimodal optical and radiological imaging agents for these aggregates. In optical imaging, neurons, glia cells and macrophages were also labeled with fluorescent protein expressed in these cells via an adeno-associated viral (AAV) vector. Longitudinal, multiscale measurements of the living mouse brains with macroscopic positron emission tomography (PET) and wide-field-of-view two-photon microscope have revealed that tau fibril injected into the brain parenchyma are transferred to the glymphatic system and subsequently to cerebral blood vessels, and this removal is mediated by astrocytes and immune cells such as perivascular macrophages. In addition, the animal PET and two-photon microscopic studies have indicated that mechanical blockade of the glymphatic flow by compression of the brain surface accelerates tau depositions in a tau transgenic model and induces neuronal alpha-synuclein accumulations in a wild-type mouse. These findings suggest that misfolded tau specie are excreted from neurons and are homeostatically cleared through the glymphatic and epidural lymphatic pathways in both normal physiological and diseased conditions, and deteriorations of these clearance processes lead to intraneuronal accumulations of fibrils composed of these proteins., 日米脳},
 title = {Neuronal dysfunction due to hyperexcitation under mild chronic cerebral hypoperfusion},
 year = {2019}
}